Efficacy and safety of ixekizumab treatment for Japanese patients with moderate to severe plaque psoriasis, erythrodermic psoriasis and generalized pustular psoriasis: Results from a 52‐week, open‐label, phase 3 study (UNCOVER‐J)

Abstract

Psoriasis, a chronic, immune‐mediated skin disease characterized by red, scaly plaques, affects approximately 0.3% of the population in Japan. The aim of this open‐label study was to evaluate the long‐term efficacy and safety of ixekizumab, a humanized, anti‐interleukin‐17A monoclonal antibody, in Japanese patients with plaque psoriasis (n = 78, including 11 psoriatic arthritis), erythrodermic psoriasis (n = 8) and generalized pustular psoriasis (n = 5). Ixekizumab was administrated s.c. at baseline (week 0, 160 mg), from weeks 2 to 12 (80 mg every 2 weeks), and from weeks 16 to 52 (80 mg every 4 weeks). At week 52, 92.3% of patients with plaque psoriasis achieved Psoriasis Area and Severity Index (PASI) 75, 80.8% achieved PASI 90, 48.7% achieved PASI 100, and 52.6% had remission of plaques (by static Physician Global Assessment, sPGA [0]). Difficult to treat areas of psoriasis (nail or scalp) also responded to ixekizumab. All patients with psoriatic arthritis who were assessed (5/5) achieved an American College of Rheumatology 20 response. Most patients with erythrodermic psoriasis or generalized pustular psoriasis responded to ixekizumab and the clinical outcome was maintained over 52 weeks (75% and 60% of patients achieved sPGA [0, 1] at week 52, respectively). Mostly mild or moderate treatment‐emergent adverse events were reported by 79 of 91 patients; the most common were nasopharyngitis, eczema, seborrheic dermatitis, urticaria and injection site reactions. In conclusion, 52‐week ixekizumab treatment was efficacious and well tolerated in Japanese patients with plaque psoriasis. Efficacy was also observed in patients with erythrodermic psoriasis, generalized pustular psoriasis and psoriatic arthritis.

Japanese guidelines for the management and treatment of generalized pustular psoriasis: The new pathogenesis and treatment of GPP

“…However, to reveal the role of biologics in the treatment of GPP from the perspective of EBM, RCT are needed to compare the efficacies of biologics and other treatment methods. However, at present, it is necessary to rely on the open‐label studies or on the accumulation of case reports because of the limited number of clinical cases and severity of disease in many cases.…”

“…In 2016, another anti‐IL‐17 antibody, ixekizumab, and an anti‐IL‐17 receptor antibody, brodalumab, were approved for health insurance coverage in Japan for patients with psoriasis vulgaris, psoriatic arthritis, pustular psoriasis and psoriatic erythroderma. The efficacy and safety of ixekizumab and brodalumab including GPP patients in an open‐label trial have been reported . Some characteristic side‐effects of IL‐17 blockage have been reported including Candida albicans infection, exacerbation of Crohn's disease and neutropenia .…”

Pathogenesis of psoriasis and development of treatment

“…IL‐17 inhibitors directly suppress the IL‐17 pathway, which is related to psoriasis. Therefore, the rates of patients attaining at least 75% improvement from baseline in the Psoriasis Area and Severity Index (PASI)‐75 and PASI‐90 were extremely high in previous studies of other biologics, and the effect was expressed rapidly . Anti‐IL‐23p19 antibody formulation for clinical use is in the final stages of development, and it has also been reported to be very effective .…”

Results of a retrospective study on the efficacy and safety of adalimumab 80 mg administrated every other week in patients with psoriasis at a single Japanese institution

“…4). [19][20][21] In patients who received ADA 80 mg every other week, 17 required switching from other biologics to ADA (IFX, 12 cases; UST, four cases; IXE, one case). 3).…”